Cohesive thin liquids to promote safe swallowing in dysphagic patients

ABSTRACT

Nutritional products having improved cohesiveness for promoting safer swallowing of food boluses for patients having swallowing conditions are provided as well as methods of making and using such products. The nutritional products may include nutritional compositions and high molecular weight, water-soluble polymers such that the nutritional products have extensional viscosities that provide improved cohesiveness to the nutritional products. Methods of administering such nutritional products to patients having impaired swallowing ability and/or dysphagia are also provided.

BACKGROUND

The present disclosure is directed to nutritional products and thetherapeutic use of these products. More specifically, the presentdisclosure is directed to nutritional products for promoting saferswallowing of food boluses for patients having swallowing conditions.

Dysphagia is the medical term for the symptom of difficulty inswallowing. Epidemiological studies estimate a prevalence rate of 16% to22% among individuals over 50 years of age.

Esophageal dysphagia affects a large number of individuals of all ages,but is generally treatable with medications and is considered a lessserious form of dysphagia. Esophageal dysphagia is often a consequenceof mucosal, mediastinal, or neuromuscular diseases. Mucosal (intrinsic)diseases narrow the lumen through inflammation, fibrosis, or neoplasiaassociated with various conditions (e.g., peptic stricture secondary togastroesophageal reflux disease, esophageal rings and webs [e.g.,sideropenic dysphagia or Plummer-Vinson syndrome], esophageal tumors,chemical injury [e.g., caustic ingestion, pill esophagitis,sclerotherapy for varices], radiation injury, infectious esophagitis,and eosinophilic esophagitis). Mediastinal (extrinsic) diseases obstructthe esophagus by direct invasion or through lymph node enlargementassociated with various conditions (tumors [e.g., lung cancer,lymphoma], infections [e.g., tuberculosis, histoplasmosis], andcardiovascular [dilated auricula and vascular compression]).Neuromuscular diseases may affect the esophageal smooth muscle and itsinnervation, disrupting peristalsis or lower esophageal sphincterrelaxation, or both, commonly associated with various conditions(achalasia [both idiopathic and associated with Chagas disease],scleroderma, other motility disorders, and a consequence of surgery[i.e., after fundoplication and antireflux interventions]). It is alsocommon for individuals with intraluminal foreign bodies to experienceacute esophageal dysphagia.

Oral pharyngeal dysphagia, on the other hand, is a very seriouscondition and is generally not treatable with medication. Oralpharyngeal dysphagia also affects individuals of all ages, but is moreprevalent in older individuals. Worldwide, oral pharyngeal dysphagiaaffects approximately 22 million people over the age of 50. Oralpharyngeal dysphagia is often a consequence of an acute event, such as astroke, brain injury, or surgery for oral or throat cancer. In addition,radiotherapy and chemotherapy may weaken the muscles and degrade thenerves associated with the physiology and nervous innervation of theswallow reflex. It is also common for individuals with progressiveneuromuscular diseases, such as Parkinson's Disease, to experienceincreasing difficulty in swallowing initiation. Representative causes oforopharyngeal dysphagia include those associated neurological illnesses(brainstem tumors, head trauma, stroke, cerebral palsy, Guillain-Barresyndrome, Huntington's disease, multiple sclerosis, polio, post-poliosyndrome, Tardive dyskinesia, metabolic encephalopathies, amyotrophiclateral sclerosis, Parkinson's disease, dementia), infectious illnesses(diphtheria, botulism, Lyme disease, syphilis, mucositis [herpetic,cytomegalovirus, candida, etc.]), autoimmune illnesses (lupus,scleroderma, Sjogren's syndrome), metabolic illnesses (amyloidosis,cushing's syndrome, thyrotoxicosis, Wilson's disease), myopathicillnesses (connective tissue disease, dermatomyositis, myastheniagravis, myotonic dystrophy, oculopharyngeal dystrophy, polymyositis,sarcoidosis, paraneoplastic syndromes, inflammatory myopathy),iatrogenic illnesses (medication side effects [e.g., chemotherapy,neuroleptics, etc.], post surgical muscular or neurogenic, radiationtherapy, corrosive [pill injury, intentional]), and structural illnesses(cricopharyngeal bar, Zenker's diverticulum, cervical webs,oropharyngeal tumors, osteophytes and skeletal abnormalities, congenital[cleft palate, diverticulae, pouches, etc.]).

Dysphagia is not generally diagnosed although the disease has majorconsequences on patient health and healthcare costs. Individuals withmore severe dysphagia generally experience a sensation of impairedpassage of food from the mouth to the stomach, occurring immediatelyafter swallowing. Among community dwelling individuals, perceivedsymptoms may bring patients to see a doctor. Among institutionalizedindividuals, health care practitioners may observe symptoms or hearcomments from the patient or his/her family member suggestive ofswallowing impairment and recommend the patient be evaluated by aspecialist. As the general awareness of swallowing impairments is lowamong front-line practitioners, dysphagia often goes undiagnosed anduntreated. Yet, through referral to a swallowing specialist (e.g.,speech language pathologist), a patient can be clinically evaluated anddysphagia diagnosis can be determined.

The general awareness of swallowing impairments is low among front-linepractitioners. Many people (especially those who are elderly) sufferwith undiagnosed and untreated swallowing impairments. One reason isthat front-line community care practitioners (e.g., generalpractitioners/geriatricians, home care nurses, physical therapists,etc.) do not typically screen for the condition. If they are aware ofthe severity of swallowing impairments, they commonly do not use anevidence-based method of screening. Furthermore, office-based assessmentof dysphagia rarely occurs.

Severity of dysphagia may vary from: (i) minimal (perceived) difficultyin safely swallowing foods and liquids, (ii) an inability to swallowwithout significant risk for aspiration or choking, and (iii) a completeinability to swallow. Commonly, the inability to properly swallow foodsand liquids may be due to food boluses being broken up into smallerfragments, which may enter the airway or leave unwanted residues in theoropharyngeal and/or esophageal tract during the swallowing process(e.g., aspiration). If enough material enters the lungs, it is possiblethat the patient may drown on the food/liquid that has built up in thelungs. Even small volumes of aspirated food may lead to bronchopneumoniainfection, and chronic aspiration may lead to bronchiectasis and maycause some cases of asthma.

“Silent aspiration,” a common condition among elderly, refers to theaspiration of the oropharyngeal contents during sleep. People maycompensate for less-severe swallowing impairments by self-limiting thediet. The aging process itself, coupled with chronic diseases such ashypertension or osteoarthritis, predisposes elderly to (subclinical)dysphagia that may go undiagnosed and untreated until a clinicalcomplication such as pneumonia, dehydration, malnutrition (and relatedcomplications) occurs. Yet, the differential diagnosis of ‘aspirationpneumonia’ is not necessarily indicated as a result of current carepractices.

The economic costs of dysphagia are associated with hospitalization,re-hospitalization, loss of reimbursement due to pay for performance(“P4P”), infections, rehabilitation, loss of work time, clinic visits,use of pharmaceuticals, labor, care taker time, childcare costs, qualityof life, increased need for skilled care. Dysphagia and aspirationimpact quality of life, morbidity and mortality. Twelve-month mortalityis high (45%) among individuals in institutional care who have dysphagiaand aspiration. The economic burden of the clinical consequences arisingfrom lack of diagnosis and early management of dysphagia aresignificant.

Pneumonia is a common clinical consequence of dysphagia. The conditionoften requires acute hospitalization and emergency room visits. Amongthose that develop pneumonia due to aspiration, the differentialdiagnosis of ‘aspiration pneumonia’ is not necessarily indicated as aresult of current care practices. Based on U.S. healthcare utilizationsurveys from recent years, pneumonia accounted for over one millionhospital discharges and an additional 392,000 were attributable toaspiration pneumonia. Individuals who have general pneumonia as theprincipal diagnosis have a mean 6 day hospital length of stay and incurover $18,000 in costs for hospital care. It is expected that aspirationpneumonia would carry higher costs for hospital care, based on a mean 8day length of hospital stay. Pneumonia is life threatening among personswith dysphagia, the odds of death within 3 months is about 50% (van derSteen et al. 2002). In addition, an acute insult such as pneumonia ofteninitiates the downward spiral in health among elderly. An insult isassociated with poor intakes and inactivity, resulting in malnutrition,functional decline, and frailty. Specific interventions (e.g., topromote oral health, help restore normal swallow, or reinforce aswallow-safe bolus) would benefit persons at risk for (due to aspirationof oropharyngeal contents, including silent aspiration) or experiencingrecurrent pneumonia.

Similar to pneumonia, dehydration is a life-threatening clinicalcomplication of dysphagia. Dehydration is a common co-morbidity amonghospitalized individuals with neurodegenerative diseases (thus, likelyto have a swallowing impairment). The conditions of Alzheimer's disease,Parkinson's disease, and multiple sclerosis account for nearly 400,000U.S. hospital discharges annually, and up to 15% of these patientssuffer dehydration. Having dehydration as the principal diagnosis isassociated with a mean 4 day length of hospital stay and over $11,000 incosts for hospital care. Nevertheless, dehydration is an avoidableclinical complication of dysphagia.

Malnutrition and related complications (e.g., [urinary tract]infections, pressure ulcers, increased severity of dysphagia [need formore-restricted food options, tube feeding, and/or PEG placement andreduced quality of life], dehydration, functional decline and relatedconsequences [falls, dementia, frailty, loss of mobility, and loss ofautonomy]) can arise when swallowing impairment leads to fear of chokingon food and liquids, slowed rate of consumption, and self-limited foodchoices. If uncorrected, inadequate nutritional intake exacerbatesdysphagia as the muscles that help facilitate normal swallow weaken asphysiological reserves are depleted. Malnutrition is associated withhaving a more than 3-times greater risk of infection. Infections arecommon in individuals with neurodegenerative diseases (thus, likely tohave a chronic swallowing impairment that jeopardizes dietary adequacy).The conditions of Alzheimer's disease, Parkinson's disease, and multiplesclerosis account for nearly 400,000 U.S. hospital discharges annually,and up to 32% of these patients suffer urinary tract infection.

Malnutrition has serious implications for patient recovery. Malnourishedpatients have longer length of hospital stay, are more likely to bere-hospitalized, and have higher costs for hospital care. Havingmalnutrition as the principal diagnosis is associated with a mean 8 daylength of hospital stay and nearly $22,000 in costs for hospital care.Furthermore, malnutrition leads to unintentional loss of weight andpredominant loss of muscle and strength, ultimately impairing mobilityand the ability to care for oneself. With the loss of functionality,caregiver burden becomes generally more severe, necessitating informalcaregivers, then formal caregivers, and then institutionalization.However, malnutrition is an avoidable clinical complication ofdysphagia.

Among persons with neurodegenerative conditions (e.g., Alzheimer'sdisease), unintentional weight loss (a marker of malnutrition) precedescognitive decline. In addition, physical activity can help stabilizecognitive health. Thus, it is important to ensure nutritional adequacyamong persons with neurodegenerative conditions to help them have thestrength and endurance to participate in regular therapeutic exerciseand guard against unintentional weight loss, muscle wasting, loss ofphysical and cognitive functionality, frailty, dementia, and progressiveincrease in caregiver burden.

Falls and related injuries are a special concern among elderly withneurodegenerative conditions, associated with loss of functionality.Falls are the leading cause of injury deaths among older adults.Furthermore, fall-related injuries among elderly accounted for more than1.8 M U.S. emergency room visits in a recent year. Direct medical coststotaled $179 M for fatal and $19.3 B for nonfatal fall-related injuriesin the period of a year. As an effect of an ambitious non-payment forperformance initiative introduced in U.S. hospitals in October 2008,Medicare will no longer pay hospitals for treatment cost of falls andrelated injuries that occur during the hospital stay. Hospitals willface a loss of about $50,000 for each elderly patient who falls andsuffers hip fracture while in hospital care. This new quality initiativeis based on the premise that falls are an avoidable medical error. Inother words, falls are preventable within reason by applyingevidence-based practices including medical nutrition therapy asnutritional interventions are efficacious in the prevention of falls andrelated injuries (e.g., fractures) among elderly.

Chewing and swallowing difficulties are also recognized risk factors forpressure ulcer development. Pressure ulcers are considered an avoidablemedical error, preventable within reason by applying evidence-basedpractices (including nutritional care, as pressure ulcers are morelikely when nutrition is inadequate). Pressure ulcers are a significantburden to the health care system. In U.S. hospitals in 2006, there were322,946 cases of medical error connected with pressure ulcerdevelopment.

The average cost of healing pressure ulcers depends on the stage,ranging from about $1,100 (for stage II) to about $10,000 (for stage III& IV pressure ulcers). Thus, the estimated cost of healing the cases ofmedical error connected with pressure ulcer development in one year, isin the range of $323 M to $3.2 B. As an effect of an ambitiousnon-payment for performance initiative introduced in U.S. hospitals inOctober 2008, Medicare will no longer pay hospitals for treatment costof pressure ulcers that develop during the hospital stay (up to $3.2 Bannually). Pressure ulcers are preventable within reason, in part, byassuring nutritional intakes are adequate. Furthermore, specificinterventions including the use of specialized nutritional supplementshelp reduce the expected time to heal pressure ulcers once they'vedeveloped.

In U.S. long-term care facilities, quality of care standards areenforced via the frequent regulatory survey. Surveyors will considerfacilities out of compliance when they uncover evidence of actual orpotential harm/negative outcomes. The range of penalties include fines,forced closure, as well as lawsuits and settlement fees. The Tag F325(nutrition) survey considers significant unplanned weight change,inadequate food/fluid intake, impairment of anticipated wound healing,failure to provide a therapeutic diet as ordered, functional decline,and fluid/electrolyte imbalance as evidence for providing sub-standard[Nutrition] care. The Tag F314 (pressure ulcers) survey mandates thatthe facility must ensure that a resident who is admitted withoutpressure ulcers does not develop pressure ulcers unless deemedunavoidable. In addition, that a resident having pressure ulcersreceives necessary treatment and services to promote healing, preventinfection and prevent new pressure ulcers from developing.

Considering the prevalence of dysphagia, possible complications relatedthereto, and the costs associated with same, it would be beneficial toprovide nutritional products that promote safer swallowing of foodboluses in patients suffering from such swallowing disorders. Suchnutritional products would improve the lives of a large and growingnumber of persons with swallowing impairments. Specific interventions(e.g., to promote oral health, help restore normal swallow, or reinforcea swallow-safe bolus) can enable persons to eat orally (vs. being tubefed and/or requiring PEG placement) and experience the psycho-socialaspects of food associated with general well being while guardingagainst the potentially negative consequences that result from lack ofadequate swallowing ability. Improvements in the intake of nutrition bydysphagic patients may also enable such patients to swallow a widervariety of food and beverage products safely and comfortably, which maylead to an overall healthier condition of the patient and preventfurther health-related decline.

SUMMARY

The present disclosure is related to nutritional products and thetherapeutic use of these products. More specifically, the presentdisclosure is related to nutritional products for promoting saferswallowing of liquids.

In a first aspect, the invention relates to a nutritional productcomprising an aqueous solution of a food grade biopolymer capable ofproviding to the nutritional product a shear viscosity of less thanabout 100 mPas, preferably of less than about 50 mPas, when measured ata shear rate of 50 s⁻¹, and a relaxation time, determined by a CapillaryBreakup Extensional Rheometry (CaBER) experiment, of more than 10 ms(milliseconds) at a temperature of 20° C.

In a preferred embodiment of the first aspect of the invention, theshear viscosity is at least about 1 mPas, preferably from at least about1 mPas to less than about 50 mPas, and more preferably from at least 5mPas to less than 20 mPas, when measured at a shear rate of 50 s⁻¹.

It is further preferred that relaxation time is less than about 2000 ms,preferably from about 20 ms to about 1000 ms, more preferably from about50 ms to about 500 ms, and most preferably from about 100 ms to about200 ms, at a temperature of 20° C.

In another preferred embodiment of the first aspect of the invention,the filament diameter of the nutritional product decreases less thanlinearly, and preferably exponentially in time during a CaBERexperiment.

It is furthermore preferred that the biopolymer is comprised in theaqueous solution in a concentration of from at least 0.01 wt % to 25 wt%, preferably from at least 0.1 wt % to 15 wt %, and most preferablyfrom at least 1 wt % to 10 wt %.

Another preferred embodiment of the first aspect of the inventionrelates to the nutritional product in diluted form, preferably in anaqueous dilution ranging from 2:1 to 50:1, more preferably from 3:1 to20:1 and most preferably from 5:1 to 10:1.

In a further preferred embodiment of the first aspect of the invention,the food grade biopolymer is selected from the group consisting ofbotanical hydrocolloids, microbial hydrocolloids, animal hydrocolloids,algae hydrocolloids and any combination thereof.

It is particularly preferred that the algae hydrocolloids are selectedfrom the group consisting of agar, carrageenan, alginate, or anycombinations thereof. In another preferred embodiment, the microbialhydrocolloids are selected from the group consisting of xanthan gum,gellan gum, curdlan gum, or any combinations thereof. In a furtherpreferred embodiment, the botanical hydrocolloids are selected from thegroup consisting of plant-extracted gums, plant-derived mucilages andcombinations thereof.

The plant-extracted gums may further be selected from the groupconsisting of okra gum, konjac mannan, tara gum, locust bean gum, guargum, fenugreek gum, tamarind gum, cassia gum, acacia gum, gum ghatti,pectins, cellulosics, tragacanth gum, karaya gum, or any combinationsthereof. In a particularly preferred embodiment of the first aspect ofthe invention, the plant-extracted gum is okra gum.

The plant-derived mucilages may preferably be selected from the groupconsisting of kiwi fruit mucilage, cactus mucilage (Ficus indica), chiaseed mucilage (Salvia hispanica), psyllium mucilage (Plantago ovata),mallow mucilage (Malva sylvestris), flax seed mucilage (Linumusitatissimum), marshmallow mucilage (Althaea officinalis), ribwortmucilage (Plantago lanceolata), mullein mucilage (Verbascum), cetrariamucilage (Lichen islandicus), or any combinations thereof. In aparticularly preferred embodiment of the first aspect of the invention,the plant-derived mucilage is kiwi fruit mucilage.

In another preferred embodiment of the first aspect of the invention,the food grade biopolymer is selected from okra gum and/or kiwi fruitmucilage, or a combination thereof. It is mostly preferred that the kiwifruit mucilage is derived from the stem pith of kiwi fruit.

In a particularly preferred embodiment of the of the first aspect of theinvention, the aqueous solution comprises rigid particles, preferablywherein the rigid particles have a size of between 1 and 100micrometers; and/or the rigid particles are comprised in an amount ofbetween 5 and 80 vol.−%; and/or the rigid particles are selected fromthe group consisting of sucrose crystals, cocoa particles,microcrystalline cellulose particles, starch and modified starchgranules, protein particles, and any combination thereof.

In an embodiment of the first aspect of the invention, the nutritionalproducts include a prebiotic. The prebiotic is preferably selected fromthe group consisting of acacia gum, alpha glucan, arabinogalactans, betaglucan, dextrans, fructooligosaccharides, fucosyllactose,galactooligosaccharides, galactomannans, gentiooligosaccharides,glucooligosaccharides, guar gum, inulin, isomaltooligosaccharides,lactoneotetraose, lactosucrose, lactulose, levan, maltodextrins, milkoligosaccharides, partially hydrolyzed guar gum, pecticoligosaccharides,resistant starches, retrograded starch, sialooligosaccharides,sialyllactose, soyoligosaccharides, sugar alcohols,xylooligosaccharides, their hydrolysates, and combinations thereof.

In another embodiment of the first aspect of the invention, thenutritional products include a probiotic. The probiotic is preferablyselected from the group consisting of Aerococcus, Aspergillus,Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces,Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc,Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus, Penicillium,Peptostrepococcus, Pichia,

Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces,Staphylococcus, Streptococcus, Torulopsis, Weissella, and combinationsthereof.

In yet another embodiment of the first aspect, the nutritional productsinclude an amino acid. The amino acid is preferably selected from thegroup consisting of alanine, arginine, asparagine, aspartate,citrulline, cysteine, glutamate, glutamine, glycine, histidine,hydroxyproline, hydroxyserine, hydroxytyrosine, hydroxylysine,isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine,taurine, threonine, tryptophan, tyrosine, valine, and combinationsthereof.

In still yet another embodiment of the first aspect of the invention,the nutritional product preferably includes a fatty acid selected fromthe group consisting of docosahexaenoic acid (DHA), eicosapentaenoicacid (EPA), and combinations thereof DHA and EPA may preferably bederived from a source selected from the group consisting of fish oil,krill, plant sources containing ω-3 fatty acids, flaxseed, walnut,algae, and combinations thereof Certain fatty acids (e.g., 18:4 fattyacids) may also be readily converted to DHA and/or EPA. The nutritionalproduct may further include α-linolenic acid.

In an embodiment of the first aspect of the invention, the nutritionalproducts include a phytonutrient, which is preferably selected from thegroup consisting of flavanoids, allied phenolic compounds, polyphenoliccompounds, terpenoids, alkaloids, sulphur-containing compounds, andcombinations thereof. In another preferred embodiment, the phytonutrientis selected from the group consisting of carotenoids, plant sterols,quercetin, curcumin, limonin, and combinations thereof.

In another preferred embodiment of the first aspect of the invention,the nutritional products include an antioxidant, which is preferablyselected from the group consisting of astaxanthin, carotenoids, coenzymeQ10 (“CoQ10”), flavonoids, glutathione Goji (wolfberry), hesperidin,lactowolfberry, lignan, lutein, lycopene, polyphenols, selenium, vitaminA, vitamin C, vitamin E, zeaxanthin, and combinations thereof.

In another embodiment of the first aspect of the invention, thenutritional product is in an administrable form selected from the groupconsisting of pharmaceutical formulations, nutritional formulations,dietary supplements, functional food and beverage products orcombinations thereof.

A second aspect of the invention relates to the use of a nutritionalproduct according to the first aspect of the invention or any of itsembodiments for treating a swallowing disorder.

In a third aspect, the invention concerns the use of a nutritionalproduct according to the first aspect of the invention or any of itsembodiments for promoting safe swallowing of nutritional products in apatient in need of same.

In a fourth aspect, the invention relates to the use of a nutritionalproduct according to the first aspect of the invention or any of itsembodiments for mitigating the risks of aspiration during swallowing ofnutritional products in a patient in need of same.

A fifth aspect of the invention pertains to a method for making anutritional product, the method comprising providing an aqueous solutionof a food grade biopolymer capable of providing to the nutritionalproduct a shear viscosity of less than about 100 mPas, preferably ofless than about 50 mPas, when measured at a shear rate of 50 s⁻¹, and arelaxation time, determined by a Capillary Breakup Extensional Rheometry(CaBER) experiment, of more than 10 ms (milliseconds) at a temperatureof 20° C.

In a preferred embodiment of this aspect, shear viscosity is at leastabout 1 mPas, preferably from at least about 1 mPas to less than about50 mPas, more preferably from at least 5 mPas to less than 20 mPas, whenmeasured at a shear rate of 50 s⁻¹.

In another preferred embodiment of the inventive method, relaxation timeis less than about 2000 ms, preferably from about 20 ms to about 1000ms, more preferably from about 50 ms to about 500 ms, and mostpreferably from about 100 ms to about 200 ms.

In a particularly preferred embodiment of the fifth aspect of theinvention, the filament diameter of the nutritional product decreasesless than linearly, and preferably exponentially in time during a CaBERexperiment.

In another preferred embodiment of the fifth aspect of the invention,the aqueous solution comprises a food grade biopolymer in aconcentration of from at least 0.01 wt % to 25 wt %, preferably from atleast 0.1 wt % to 15 wt %, and most preferably from at least 1 wt % to10 wt %.

In another embodiment, the method according to the fifth aspect of theinvention further comprises the step of diluting the nutritionalproduct, preferably in an aqueous dilution ranging from 2:1 to 50:1,more preferably from 3:1 to 20:1 and most preferably from 5:1 to 10:1.

In yet another embodiment of the fifth aspect, the food grade biopolymeris selected from the group consisting of botanical hydrocolloids,microbial hydrocolloids, animal hydrocolloids, algae hydrocolloids andany combination thereof.

In still yet another embodiment of the fifth aspect of the invention,the algae hydrocolloids are selected from the group consisting of agar,carrageenan, alginate, or any combinations thereof. In anotherembodiment of said aspect, the microbial hydrocolloids are selected fromthe group consisting of xanthan gum, gellan gum, curdlan gum, or anycombinations thereof. In a further embodiment of said aspect, thebotanical hydrocolloids are selected from the group consisting ofplant-extracted gums, plant-derived mucilages and combinations thereof.

A preferred embodiment of the invention relates to the method accordingto the fifth aspect, wherein the plant-extracted gums are selected fromthe group consisting of okra gum, konjac mannan, tara gum, locust beangum, guar gum, fenugreek gum, tamarind gum, cassia gum, acacia gum, gumghatti, pectins, cellulosics, tragacanth gum, karaya gum, or anycombinations thereof. In a particularly preferred embodiment thereof,the plant-extracted gum is okra gum.

Another preferred embodiment of the invention relates to the methodaccording to the fifth aspect, wherein the plant-derived mucilages areselected from the group consisting of kiwi fruit mucilage, cactusmucilage (Ficus indica), chia seed mucilage (Salvia hispanica), psylliummucilage (Plantago ovata), mallow mucilage (Malva sylvestris), flax seedmucilage (Linum usitatissimum), marshmallow mucilage (Althaeaofficinalis), ribwort mucilage (Plantago lanceolata), mullein mucilage(Verbascum), cetraria mucilage (Lichen islandicus), or any combinationsthereof. In a particularly preferred embodiment thereof, theplant-derived mucilage is kiwi fruit mucilage.

In a further preferred embodiment of the method of the invention, thefood grade biopolymer is selected from okra gum and/or kiwi fruitmucilage, or a combination thereof. It is mostly preferred that in thismethod, the kiwi fruit mucilage is derived from the stem pith of kiwifruit.

In a particularly preferred embodiment of the of the fifth aspect of theinvention, the aqueous solution comprises rigid particles, preferablywherein the rigid particles have a size of between 1 and 100micrometers; and/or the rigid particles are comprised in an amount ofbetween 5 and 80 vol.−%; and/or the rigid particles are selected fromthe group consisting of sucrose crystals, cocoa particles,microcrystalline cellulose particles, starch and modified starchgranules, protein particles, and any combination thereof.

In a further embodiment of the fifth aspect of the invention, theinventive method further comprises adding to the nutritional product aprebiotic, which is preferably selected from the group consisting ofacacia gum, alpha glucan, arabinogalactans, beta glucan, dextrans,fructooligosaccharides, fucosyllactose, galactooligosaccharides,galactomannans, gentiooligosaccharides, glucooligosaccharides, guar gum,inulin, isomaltooligosaccharides, lactoneotetraose, lactosucrose,lactulose, levan, maltodextrins, milk oligosaccharides, partiallyhydrolyzed guar gum, pecticoligosaccharides, resistant starches,retrograded starch, sialooligosaccharides, sialyllactose,soyoligosaccharides, sugar alcohols, xylooligosaccharides, theirhydrolysates, and combinations thereof.

In a further embodiment of the fifth aspect of the invention, theinventive method further comprises adding to the nutritional products aprobiotic, which is preferably selected from the group consisting ofAerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida,Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus,Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus,Pediococcus, Penicillium, Peptostrepococcus, Pichia, Propionibacterium,Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus,Streptococcus, Torulopsis, Weissella, and combinations thereof.

In a further embodiment of the fifth aspect of the invention, theinventive method further comprises adding to the nutritional products anamino acid, which is preferably selected from the group consisting ofalanine, arginine, asparagine, aspartate, citrulline, cysteine,glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyserine,hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine,phenylalanine, proline, serine, taurine, threonine, tryptophan,tyrosine, valine, and combinations thereof.

In a further embodiment of the fifth aspect of the invention, theinventive method further comprises adding to the nutritional product afatty acid preferably selected from the group consisting ofdocosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), andcombinations thereof. DHA and EPA may also be derived from a sourceselected from the group consisting of fish oil, krill, plant sourcescontaining ω-3 fatty acids, flaxseed, walnut, algae, and combinationsthereof. Certain fatty acids (e.g., 18:4 fatty acids) may also bereadily converted to DHA and/or EPA. The above method may furtherinclude adding to the nutritional product an α-linolenic acid.

In a further embodiment of the fifth aspect of the invention, theinventive method further comprises adding to the nutritional products aphytonutrient selected from the group consisting of flavanoids, alliedphenolic compounds, polyphenolic compounds, terpenoids, alkaloids,sulphur-containing compounds, and combinations thereof It is furtherpreferred that the phytonutrient is selected from the group consistingof carotenoids, plant sterols, quercetin, curcumin, limonin, andcombinations thereof.

In an embodiment, the method according to the fifth aspect of theinvention further comprises adding to the nutritional product anantioxidant selected from the group consisting of astaxanthin,carotenoids, coenzyme Q10 (“CoQ10”), flavonoids, glutathione Goji(wolfberry), hesperidin, lactowolfberry, lignan, lutein, lycopene,polyphenols, selenium, vitamin A, vitamin C, vitamin E, zeaxanthin, andcombinations thereof.

In another embodiment, the method of the invention further comprises thestep of bringing the nutritional products in an administrable form,which is preferably selected from the group consisting of pharmaceuticalformulations, nutritional formulations, dietary supplements, functionalfood and beverage products or combinations thereof.

An advantage of the above aspects one to five of the invention and theirembodiments is to provide improved nutritional products, and inparticular to provide improved liquid nutritional products.

A particular advantage of these aspects and embodiments is to provideimproved nutritional products for patients having dysphagia.

Yet another particular advantage of the above aspects and embodiments ofthe invention is to provide nutritional products that are useful fortreating patients having dysphagia.

Yet another advantage of the above aspects and embodiments of theinvention is to provide nutritional products that are useful forpromoting safe swallowing of food boluses.

Additional features and advantages are described herein, and will beapparent from the following Detailed Description.

DETAILED DESCRIPTION

As used herein, “about” is understood to refer to numbers in a range ofnumerals. Moreover, all numerical ranges herein should be understood toinclude all integer, whole or fractions, within the range.

As used herein, “wt %” is understood to refer to the weight of polymerper total weight of the product.

The term “amino acid” is understood to include one or more amino acids.The amino acid can be, for example, alanine, arginine, asparagine,aspartate, citrulline, cysteine, glutamate, glutamine, glycine,histidine, hydroxyproline, hydroxyserine, hydroxytyrosine,hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine,proline, serine, taurine, threonine, tryptophan, tyrosine, valine, orcombinations thereof.

As used herein, “animal” includes, but is not limited to, mammals, whichinclude but is not limited to, rodents, aquatic mammals, domesticanimals such as dogs and cats, farm animals such as sheep, pigs, cowsand horses, and humans. Wherein the terms “animal” or “mammal” or theirplurals are used, it is contemplated that it also applies to any animalsthat are capable of the effect exhibited or intended to be exhibited bythe context of the passage.

As used herein, the term “antioxidant” is understood to include any oneor more of various substances such as beta-carotene (a vitamin Aprecursor), vitamin C, vitamin E, and selenium that inhibit oxidation orreactions promoted by Reactive Oxygen Species (“ROS”) and other radicaland non-radical species. Additionally, antioxidants are moleculescapable of slowing or preventing the oxidation of other molecules.Non-limiting examples of antioxidants include carotenoids, coenzyme Q10(“CoQ10”), flavonoids, glutathione Goji (wolfberry), hesperidin,lactowolfberry, lignan, lutein, lycopene, polyphenols, selenium, vitaminA, vitamin B₁, vitamin B₆, vitamin B₁₂, vitamin C, vitamin D, vitamin E,zeaxanthin, or combinations thereof.

While the terms “individual” and “patient” are often used herein torefer to a human, the invention is not so limited. Accordingly, theterms “individual” and “patient” refer to any animal, mammal or humanhaving or at risk for a medical condition that can benefit from thetreatment.

As used herein, non-limiting examples of sources of ω-3 fatty acids suchα-linolenic acid (“ALA”), docosahexaenoic acid (“DHA”) andeicosapentaenoic acid (“EPA”) include fish oil, krill, poultry, eggs, orother plant or nut sources such as flax seed, walnuts, almonds, algae,modified plants, etc.

As used herein, “food grade micro-organisms” means micro-organisms thatare used and generally regarded as safe for use in food.

As used herein, “mammal” includes, but is not limited to, rodents,aquatic mammals, domestic animals such as dogs and cats, farm animalssuch as sheep, pigs, cows and horses, and humans. Wherein the term“mammal” is used, it is contemplated that it also applies to otheranimals that are capable of the effect exhibited or intended to beexhibited by the mammal.

The term “microorganism” is meant to include the bacterium, yeast and/orfungi, a cell growth medium with the microorganism, or a cell growthmedium in which microorganism was cultivated.

As used herein, the term “minerals” is understood to include boron,calcium, chromium, copper, iodine, iron, magnesium, manganese,molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin,vanadium, zinc, or combinations thereof.

As used herein, a “non-replicating” microorganism means that no viablecells and/or colony forming units can be detected by classical platingmethods. Such classical plating methods are summarized in themicrobiology book: James Monroe Jay, et al., Modern food microbiology,7th edition, Springer Science, New York, N.Y. p. 790 (2005). Typically,the absence of viable cells can be shown as follows: no visible colonyon agar plates or no increasing turbidity in liquid growth medium afterinoculation with different concentrations of bacterial preparations(‘non replicating’ samples) and incubation under appropriate conditions(aerobic and/or anaerobic atmosphere for at least 24 h). For example,bifidobacteria such as Bifidobacterium longum, Bifidobacterium lactisand Bifidobacterium breve or lactobacilli, such as Lactobacillusparacasei or Lactobacillus rhamnosus, may be rendered non-replicating byheat treatment, in particular low temperature/long time heat treatment.

As used herein, a “nucleotide” is understood to be a subunit ofdeoxyribonucleic acid (“DNA”) or ribonucleic acid (“RNA”). It is anorganic compound made up of a nitrogenous base, a phosphate molecule,and a sugar molecule (deoxyribose in DNA and ribose in RNA). Individualnucleotide monomers (single units) are linked together to form polymers,or long chains. Exogenous nucleotides are specifically provided bydietary supplementation. The exogenous nucleotide can be in a monomericform such as, for example, 5′-Adenosine

Monophosphate (“5′-AMP”), 5′-Guanosine Monophosphate (“5′-GMP”),5′-Cytosine Monophosphate (“5′-CMP”), 5′-Uracil Monophosphate(“5′-UMP”), 5′-Inosine Monophosphate (“5′-IMP”), 5′-ThymineMonophosphate (“5′-TMP”), or combinations thereof. The exogenousnucleotide can also be in a polymeric form such as, for example, anintact RNA. There can be multiple sources of the polymeric form such as,for example, yeast RNA.

“Nutritional compositions,” as used herein, are understood to includeany number of optional additional ingredients, including conventionalfood additives, for example one or more, acidulants, additionalthickeners, buffers or agents for pH adjustment, chelating agents,colorants, emulsifies, excipient, flavor agent, mineral, osmotic agents,a pharmaceutically acceptable carrier, preservatives, stabilizers,sugar, sweeteners, texturizers, and/or vitamins. The optionalingredients can be added in any suitable amount.

As used herein the term “patient” is understood to include an animal,especially a mammal, and more especially a human that is receiving orintended to receive treatment, as it is herein defined.

As used herein, “phytochemicals” or “phytonutrients” are non-nutritivecompounds that are found in many foods. Phytochemicals are functionalfoods that have health benefits beyond basic nutrition, and are healthpromoting compounds that come from plant sources. “Phytochemicals” and“Phytonutrients” refers to any chemical produced by a plant that impartsone or more health benefit on the user. Non-limiting examples ofphytochemicals and phytonutrients include those that are:

i) phenolic compounds which include monophenols (such as, for example,apiole, carnosol, carvacrol, dillapiole, rosemarinol); flavonoids(polyphenols) including flavonols (such as, for example, quercetin,fingerol, kaempferol, myricetin, rutin, isorhamnetin), flavanones (suchas, for example, fesperidin, naringenin, silybin, eriodictyol), flavones(such as, for example, apigenin, tangeritin, luteolin), flavan-3-ols(such as, for example, catechins, (+)-catechin, (+)-galloc ate chin,(−)-epicat echin, (−)-epigallocatechin, (−)-epigallocatechin gallate(EGCG), (−)-epicatechin 3-gallate, theaflavin, theaflavin-3-gallate,theaflavin-3′-gallate, theaflavin-3,3′-digallate, thearubigins),anthocyanins (flavonals) and anthocyanidins (such as, for example,pelargonidin, peonidin, cyanidin, delphinidin, malvidin, petunidin),isoflavones (phytoestrogens) (such as, for example, daidzein(formononetin), genistein (biochanin A), glycitein), dihydroflavonols,chalcones, coumestans (phytoestrogens), and Coumestrol; Phenolic acids(such as: Ellagic acid, Gallic acid, Tannic acid, Vanillin, curcumin);hydroxycinnamic acids (such as, for example, caffeic acid, chlorogenicacid, cinnamic acid, ferulic acid, coumarin); lignans (phytoestrogens),silymarin, secoisolariciresinol, pinoresinol and lariciresinol); tyrosolesters (such as, for example, tyrosol, hydroxytyrosol, oleocanthal,oleuropein); stilbenoids (such as, for example, resveratrol,pterostilbene, piceatannol) and punicalagins;

ii) terpenes (isoprenoids) which include carotenoids (tetraterpenoids)including carotenes (such as, for example, α-carotene, β-carotene,γ-carotene, δ-carotene, lycopene, neurosporene, phytofluene, phytoene),and xanthophylls (such as, for example, canthaxanthin, cryptoxanthin,aeaxanthin, astaxanthin, lutein, rubixanthin); monoterpenes (such as,for example, limonene, perillyl alcohol); saponins; lipids including:phytosterols (such as, for example, campesterol, beta sitosterol, gammasitosterol, stigmasterol), tocopherols (vitamin E), and ω-3, -6, and -9fatty acids (such as, for example, gamma-linolenic acid); triterpenoid(such as, for example, oleanolic acid, ursolic acid, betulinic acid,moronic acid);

iii) betalains which include Betacyanins (such as: betanin, isobetanin,probetanin, neobetanin); and betaxanthins (non glycosidic versions)(such as, for example, indicaxanthin, and vulgaxanthin);

iv) organosulfides, which include, for example, dithiolthiones(isothiocyanates) (such as, for example, sulphoraphane); andthiosulphonates (allium compounds) (such as, for example, allyl methyltrisulfide, and diallyl sulfide), indoles, glucosinolates, whichinclude, for example, indole-3-carbinol; sulforaphane;3,3′-diindolylmethane; sinigrin; allicin; alliin; allyl isothiocyanate;piperine; syn-propanethial-S-oxide;

v) protein inhibitors, which include, for example, protease inhibitors;

vi) other organic acids which include oxalic acid, phytic acid (inositolhexaphosphate); tartaric acid; and anacardic acid; or

vii) combinations thereof.

As used in this disclosure and the appended claims, the singular forms“a,” “an” and “the” include plural referents unless the context clearlydictates otherwise. Thus, for example, reference to “a polypeptide”includes a mixture of two or more polypeptides, and the like.

As used herein, a “prebiotic” is a food substance that selectivelypromotes the growth of beneficial bacteria or inhibits the growth ormucosal adhesion of pathogenic bacteria in the intestines. They are notinactivated in the stomach and/or upper intestine or absorbed in thegastrointestinal tract of the person ingesting them, but they arefermented by the gastrointestinal microflora and/or by probiotics.Prebiotics are, for example, defined by Glenn R. Gibson and Marcel B.Roberfroid, Dietary Modulation of the Human Colonic Microbiota:Introducing the Concept of Prebiotics, J. Nutr. 1995 125: 1401-1412.Non-limiting examples of prebiotics include acacia gum, alpha glucan,arabinogalactans, beta glucan, dextrans, fructooligosaccharides,fucosyllactose, galactooligosaccharides, galactomannans,gentiooligosaccharides, glucooligosaccharides, guar gum, inulin,isomaltooligosaccharides, lactoneotetraose, lactosucrose, lactulose,levan, maltodextrins, milk oligosaccharides, partially hydrolyzed guargum, pecticoligosaccharides, resistant starches, retrograded starch,sialooligosaccharides, sialyllactose, soyoligosaccharides, sugaralcohols, xylooligosaccharides, or their hydrolysates, or combinationsthereof.

As used herein, probiotic micro-organisms (hereinafter “probiotics”) arefood-grade microorganisms (alive, including semi-viable or weakened,and/or non-replicating), metabolites, microbial cell preparations orcomponents of microbial cells that could confer health benefits on thehost when administered in adequate amounts, more specifically, thatbeneficially affect a host by improving its intestinal microbialbalance, leading to effects on the health or well-being of the host.See, Salminen S, Ouwehand A. Benno Y. et al., Probiotics: how shouldthey be defined?, Trends Food Sci. Technol. 1999:10, 107-10. In general,it is believed that these micro-organisms inhibit or influence thegrowth and/or metabolism of pathogenic bacteria in the intestinal tract.The probiotics may also activate the immune function of the host. Forthis reason, there have been many different approaches to includeprobiotics into food products. Non-limiting examples of probioticsinclude Aerococcus, Aspergillus, Bacillus, Bacteroides, Bifidobacterium,Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium,Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Micrococcus,Mucor, Oenococcus, Pediococcus, Penicillium, Peptostrepococcus, Pichia,Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces,Staphylococcus, Streptococcus, Torulopsis, Weissella, or combinationsthereof

The terms “protein,” “peptide,” “oligopeptides” or “polypeptide,” asused herein, are understood to refer to any composition that includes, asingle amino acids (monomers), two or more amino acids joined togetherby a peptide bond (dipeptide, tripeptide, or polypeptide), collagen,precursor, homolog, analog, mimetic, salt, prodrug, metabolite, orfragment thereof or combinations thereof For the sake of clarity, theuse of any of the above terms is interchangeable unless otherwisespecified. It will be appreciated that polypeptides (or peptides orproteins or oligopeptides) often contain amino acids other than the 20amino acids commonly referred to as the 20 naturally occurring aminoacids, and that many amino acids, including the terminal amino acids,may be modified in a given polypeptide, either by natural processes suchas glycosylation and other post-translational modifications, or bychemical modification techniques which are well known in the art. Amongthe known modifications which may be present in polypeptides of thepresent invention include, but are not limited to, acetylation,acylation, ADP-ribosylation, amidation, covalent attachment of aflavanoid or a heme moiety, covalent attachment of a polynucleotide orpolynucleotide derivative, covalent attachment of a lipid or lipidderivative, covalent attachment of phosphatidylinositol, cross-linking,cyclization, disulfide bond formation, demethylation, formation ofcovalent cross-links, formation of cystine, formation of pyro glutamate,formylation, gamma-carboxylation, glycation, glycosylation,glycosylphosphatidyl inositol (“GPI”) membrane anchor formation,hydroxylation, iodination, methylation, myristoylation, oxidation,proteolytic processing, phosphorylation, prenylation, racemization,selenoylation, sulfation, transfer-RNA mediated addition of amino acidsto polypeptides such as arginylation, and ubiquitination. The term“protein” also includes “artificial proteins” which refers to linear ornon-linear polypeptides, consisting of alternating repeats of a peptide.

Non-limiting examples of proteins include dairy based proteins, plantbased proteins, animal based proteins and artificial proteins. Dairybased proteins include, for example, casein, caseinates (e.g., all formsincluding sodium, calcium, potassium caseinates), casein hydrolysates,whey (e.g., all forms including concentrate, isolate, demineralized),whey hydrolysates, milk protein concentrate, and milk protein isolate.Plant based proteins include, for example, soy protein (e.g., all formsincluding concentrate and isolate), pea protein (e.g., all formsincluding concentrate and isolate), canola protein (e.g., all formsincluding concentrate and isolate), other plant proteins thatcommercially are wheat and fractionated wheat proteins, corn and itfractions including zein, rice, oat, potato, peanut, green pea powder,green bean powder, and any proteins derived from beans, lentils, andpulses. Animal based proteins may be selected from the group consistingof beef, poultry, fish, lamb, seafood, or combinations thereof.

All dosage ranges contained within this application are intended toinclude all numbers, whole or fractions, contained within said range.

As used herein, a “synbiotic” is a supplement that contains both aprebiotic and a probiotic that work together to improve the microfloraof the intestine.

As used herein, the terms “treatment,” “treat” and “to alleviate”include both prophylactic or preventive treatment (that prevent and/orslow the development of a targeted pathologic condition or disorder) andcurative, therapeutic or disease-modifying treatment, includingtherapeutic measures that cure, slow down, lessen symptoms of, and/orhalt progression of a diagnosed pathologic condition or disorder; andtreatment of patients at risk of contracting a disease or suspected tohave contracted a disease, as well as patients who are ill or have beendiagnosed as suffering from a disease or medical condition. The termdoes not necessarily imply that a subject is treated until totalrecovery. The terms “treatment” and “treat” also refer to themaintenance and/or promotion of health in an individual not sufferingfrom a disease but who may be susceptible to the development of anunhealthy condition, such as nitrogen imbalance or muscle loss. Theterms “treatment,” “treat” and “to alleviate” are also intended toinclude the potentiation or otherwise enhancement of one or more primaryprophylactic or therapeutic measure. The terms “treatment,” “treat” and“to alleviate” are further intended to include the dietary management ofa disease or condition or the dietary management for prophylaxis orprevention a disease or condition.

As used herein the term “vitamin” is understood to include any ofvarious fat-soluble or water-soluble organic substances (non-limitingexamples include vitamin A, Vitamin B1 (thiamine), Vitamin B2(riboflavin), Vitamin B3 (niacin or niacinamide), Vitamin B5(pantothenic acid), Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine,or pyridoxine hydrochloride), Vitamin B7 (biotin), Vitamin B9 (folicacid), and Vitamin B12 (various cobalamins; commonly cyanocobalamin invitamin supplements), vitamin C, vitamin D, vitamin E, vitamin K, folicacid and biotin) essential in minute amounts for normal growth andactivity of the body and obtained naturally from plant and animal foodsor synthetically made, pro-vitamins, derivatives, analogs.

The present disclosure relates to nutritional products for promotingsafer swallowing of food boluses for patients suffering from swallowingdisorders including, for example, dysphagia. The present disclosure alsorelates to methods for providing treatment for a patient having aswallowing disorder.

The normal swallowing of a human (or mammal) involves three distinctphases which are interdependent and well coordinated: (i) the oral, (ii)the pharyngeal, and (iii) the esophageal phases. In the oral phase,which is under voluntary control, food that has been chewed and mixedwith saliva is formed into a bolus for delivery by voluntary tonguemovements to the back of the mouth, into the pharynx. The pharyngealphase is involuntary and is triggered by food/liquid bolus passingthrough the faucial pillars into the pharynx. Contraction of the threeconstrictors of the pharynx propel the bolus towards the upperesophageal sphincter. Simultaneously, the soft palate closes thenasopharynx. The larynx moves upwards to prevent food or liquid passinginto the airway, which is aided by the backward tilt of the epiglottisand closure of the vocal folds. The esophageal phase is also involuntaryand starts with the relaxation of the upper esophageal sphincterfollowed by peristalsis, which pushes the bolus down to the stomach.

Dysphagia refers to the symptom of difficulty in swallowing. Thefollowing general causes of dysphagia have been identified:

-   a) A decreased ability to swallow-   b) Tongue not exerting enough pressure on soft palate    -   i) Iatrogenic        -   (1) Surgical removal of part of the tongue or soft palate            -   (a) Treatment for snoring or sleep apnea            -   (b) Resection due to tumor (malignant or benign)    -   ii) Genetic        -   (1) Hypoplasia of the tongue and/or soft palate        -   (2) Hypo or lack of innervation to tongue and/or soft palate    -   iii) Traumatic        -   (1) Tissue damage        -   (2) Deinnervation/hypoinnervation    -   iv) Neurologic        -   (1) Local deinnervation/hypoinnervation        -   (2) CNS            -   (a) Post stroke            -   (b) Demylination-   c) Abnormal epiglottis behavior    -   i) Not closing and opening at proper times        -   (1) Opening too early        -   (2) Not closing in time            -   (a) Delayed closing    -   ii) Not closing completely (insufficient flexibility—atrophy)

The consequences of untreated or poorly managed oral pharyngealdysphagia can be severe, including dehydration, malnutrition leading todysfunctional immune response, and reduced functionality, airwayobstruction with solid foods (choking), and airway aspiration of liquidsand semi-solid foods, promoting aspiration pneumonia and/or pneumonitis.Severe oral pharyngeal dysphagia may require nutrition to be supplied bytube feeding.

Mild to moderate oral pharyngeal dysphagia may require the texture offoods to be modified in order to minimize the likelihood of choking oraspiration. This may include the thickening of liquids and/or pureeingof solid foods, both of which have been shown to be the most effectivemeans of preventing choking and aspiration during the eating process.Thickened liquids are designed to have three properties: (i) a morecohesive bolus that can be maintained throughout the action ofswallowing, (ii) slower delivery to the throat, thereby compensating forthe increased period in which the swallowing reflexes prepare for thethickened liquid, and (iii) provide greater density to increaseawareness of the presence of food or liquid bolus in the mouth.

Improving an individual's ability and efficiency to swallow improves theindividual's safety through reduced risk of pulmonary aspiration. Anefficient swallow may permit greater independence from feedingassistance and/or reduced length of time spent in feeding-assistanceduring meal consumption. Efficient swallowing also reduces the viscosityof liquids required for safety (e.g., pudding, honey and nectarthickness products) and may also limit the use of texture-modifiedfoods. All of these previously described factors are aimed at improvingan individual's quality of life.

Therefore, the present disclosure provides nutritional products forpromoting safer swallowing of food boluses in patients with swallowingdisorders (e.g., dysphagic patients) by preventing bolus penetration andaspiration through modification of rheological properties of foods andbeverages.

The nutritional products of the present invention comprise an aqueoussolution of a food grade biopolymer, which is capable of providing tothe nutritional product a shear viscosity of less than about 100 mPas,preferably of less than about 50 mPas, when measured at a shear rate of50 s⁻¹, and a relaxation time, determined by a Capillary BreakupExtensional Rheometry (CaBER) experiment, of more than 10 ms(milliseconds) at a temperature of 20° C.

Rheology is the study of the flow of matter, primarily in the liquidstate but also as soft solids or solids under conditions in which theyrespond with plastic flow rather than deforming elastically in responseto an applied force. The flow of substances cannot generally becharacterized by a single value of viscosity, although viscositymeasurements at specific temperatures can provide valuable informationabout a material's properties. A commonly measured rheological propertyof a material is it's shear viscosity. Shear viscosity, often referredto as simply viscosity, describes the reaction of a material to appliedshear stress. In other words, shear stress is the ratio between “stress”(force per unit area) exerted on the surface of a fluid, in the lateralor horizontal direction, to the change in velocity of the fluid as youmove down in the fluid (a “velocity gradient”). In a preferredembodiment of the nutritional product of the present invention, theshear viscosity is at least about 1 mPas, preferably from at least about1 mPas to less than about 50 mPas, and more preferably from at least 5mPas to less than 20 mPas, when measured at a shear rate of 50 s⁻¹.

Another rheological property of a material is its extensional viscosity.Extensional viscosity is the ratio of the stress required to extend aliquid in its flow direction to the extension rate. Extensionalviscosity coefficients are widely used for characterizing polymers,where they cannot be simply calculated or estimated from the shearviscosity. Rheological studies are generally performed using rheometers,which generally impose a specific stress field or deformation to thefluid and monitor the resultant deformation or stress. These instrumentsmay operate in steady flow or oscillatory flow, as well as both shearand extension.

The herein used Capillary Breakup Extensional Rheometer (CaBER) is anexample for a rheometer applying extensional stress. During the CaBERexperiment as performed herein for measuring the relaxation time of thenutritional product, a drop of said product is placed between twovertically aligned and parallel circular metal surfaces, both having adiameter of 6 mm. The metal surfaces are then rapidly separated linearlyover a time interval of 50 ms (milliseconds). The filament formed bythis stretching action subsequently thins under the action ofinterfacial tension and the thinning process is followed quantitativelyusing a laser sheet measuring the filament diameter at its mid-point.The relaxation time in a CaBER experiment is determined by plotting thenormalised natural logarithm of the filament diameter during thethinning process versus time and determining the slope of the linearportion (dln (D/D0)/dt) of this curve, where D is the filament diameter,D0 the filament diameter at time zero and t the time of filamentthinning. The relaxation time in this context is then defined as minusone third (−⅓) times the inverse of this slope, i.e. −1/(3dln(D/D0)/dt).

In an embodiment of the inventive nutritional product, the thusdetermined relaxation time is less than about 2000 ms, preferably fromabout 20 ms to about 1000 ms, more preferably from about 50 ms to about500 ms, and most preferably from about 100 ms to about 200 ms, at atemperature of 20° C. It is furthermore preferred that the filamentdiameter of the nutritional product decreases less than linearly, andpreferably exponentially in time during a CaBER experiment.

During processing in the mouth and swallowing, the viscosity of a foodproduct changes due to shear forces. It is generally known that theviscosity of a food product decreases when the shear forces and rateacting on the food product (e.g., chewing forces) increase. A knowtreatment for beverages and liquid foods is to increase the viscosity ofthe food/beverage by adding starch or gum thickeners. Such thickening isthought to improve bolus control and timing of swallowing. It is,however, often disliked by patients because of the extra swallowingeffort and may also leave residues at high levels of viscosity. Forsolid foods, pureed diets are often described when problems withmastication and swallowing of solid pieces occur in patients. However,these pureed diets may lack the natural cohesiveness that salivaprovides to “real” food boluses.

Extensional viscosity is generally only relevant in flows where a fluidis “stretched”/extended (e.g., when a flowing through a constrictionsuch as an esophageal sphincter), or when compressed (e.g., between thetongue and plate or the tongue and pharynx). However, any compressiveforce also implies an extension (e.g., in another direction). Only inso-called “simple shear” flows, like in a straight pipe would the shearviscosity alone determine the fluid flow. In a process like swallowing,most steps of the bolus transport will have a certain degree ofextension as well. The difference between shear and extensionalviscosity is usually expressed in terms of a “Trouton ratio,” which isthe ratio between the extensional viscosity and the shear viscosity atthe same rate of deformation and as expressed in reciprocal seconds.

As such, and as opposed to the effects of shear viscosity, thenutritional products of the present disclosure aim to improve thecohesion of food boluses to prevent a food bolus from being broken upinto smaller fragments, which may enter the airway or leave unwantedresidues in the oropharyngeal and/or esophageal tract during theswallowing process. Salivary proteins appear to naturally have thisfunction of increasing the cohesiveness of a food bolus. Applicants havesurprisingly found that the incorporation of food grade biopolymers innutritional products achieve a similar or identical, possibly evenenhanced effect of increasing the cohesiveness of the food bolus (e.g.,for patients who have compromised secretion of saliva). This principlemay be applicable both to beverages, in which such polymers may bedissolved, and semi-solid foodstuffs (e.g., purees) which need tomaintain sufficient integrity to be safely swallowed and where solid andsemi-solid particles are held together by a “cohesive” aqueous phasecontaining such polymers.

In the nutritional product of the present invention, the aqueoussolution preferably comprises such a food grade biopolymer in aconcentration of from at least 0.01 wt % to 25 wt %, preferably from atleast 0.1 wt % to 15 wt %, and most preferably from at least 1 wt % to10 wt %. All percentages given in this specifications refer to theweight of polymer per total weight of the product (wt %).

Another embodiment of the present invention relates to the inventivenutritional product in diluted form, preferably in an aqueous dilutionranging from 2:1 to 50:1, more preferably from 3:1 to 20:1 and mostpreferably from 5:1 to 10:1. By way of example, a dilution of 2:1 meansthat 1 part of nutritional product is diluted in 2 parts of water.

Applicants have also found that providing nutritional products todysphagic patients having increased bolus cohesion due to itsextensional viscosity, without dramatically modifying other physicalproperties of the material such as, for example, its shear viscosity,dramatically reduces the amount of swallowing effort for the patient, aswell as the risk of residue build-up in the oropharyngeal and/oresophageal tracts. As such, products having increased cohesivenessprovide improved nutritional intake of dysphagic patients by enablingthem to swallow a wider variety of food and beverage products safely andcomfortably. This is achieved by improving bolus integrity(“cohesiveness”) and thus lending confidence to the patient in beingable to consume the different products. The nutritional improvementachieved by an improved food and water intake may lead to an overallhealthier condition of the patient and prevent further decline.

The polymers included in the present nutritional products may includeany high molecular weight, water-soluble biopolymer that is capable ofenhancing the extensional viscosity and, thus, the cohesiveness (e.g.,resistance to break-up) of the nutritional products. Such polymers mayinclude, for example, botanical hydrocolloids, microbial hydrocolloids,animal hydrocolloids and algae hydrocolloids.

Algae hydrocolloids that may be used in the present nutritional productsmay include, for example, agar, carrageenan, alginate or combinationsthereof. Microbial hydrocolloids that may be used in the nutritionalproducts of the invention may be selected from xanthan gum, gellan gum,curdlan gum, or combinations thereof. The botanical hydrocolloids thatmay be included in the present nutritional products may be selected fromplant-extracted gums, plant-derived mucilages, and combinations thereof.

Gums that may be used in the present nutritional products may include,for example, okra gum, glucomannans (konjac mannan), galactomannans(tara gum, locust bean gum, guar gum, fenugreek gum), tamarind gum,cassia gum, gum Arabic (acacia gum), gum ghatti, pectin, cellulosics,tragacanth gum, karaya gum, and combinations thereof, wherein Okra gumis preferred.

In the context of this disclosure, the gums are preferably food gradeand can be commercially obtained from numerous suppliers. For example,Xanthan gum is a high molecular weight, long chain polysaccharidecomposed of the sugars glucose, mannose, and glucuronic acid. Thebackbone is similar to cellulose, with added side chains oftrisaccharides. Galactomannans are polysaccharides made of a mannosebackbone with (single) side chains of galactose units. The ratio ofgalactose to mannose differs in different galactomannans, with usuallythe majority being mannose. Glucomannans are polysaccharides mainlyunbranched with a backbone comprised of D-glucose and D-mannoseresidues. Usually approximately 60% of the polysaccharide is made up ofD-mannose and approximately 40% of D-glucose. In the context of thepresent disclosure, galactomannans and glucomannans are food grade andcan be commercially obtained from numerous suppliers.

Mucilages that may be used in the present nutritional products mayinclude, for example, kiwi fruit mucilage, cactus mucilage, chia seedmucilage, psyllium mucilage, mallow mucilage, flax seed mucilage,marshmallow mucilage, ribwort mucilage, mullein mucilage, cetrariamucilage, or combinations thereof. In a preferred embodiment of theinventive nutritional product, the food grade polymer is selected fromokra gum and/or kiwi fruit mucilage, or a combination thereof.

It is particularly preferred that the plant-derived mucilage is kiwifruit mucilage. Said mucilage is most preferably derived from the stempith of kiwi fruit. The stem of kiwi fruit, which typically representsthe plant waste material remaining from kiwi fruit agriculture, containsabout 20% of mucilage.

In the context of this disclosure, also the mucilages are preferablyfood grade and can be commercially obtained from numerous suppliers.

Moreover, according to the present invention, the gums and mucilages maybe obtained by any suitable extraction method known in the art. Ageneral protocol for extracting gums and mucilages involves soaking theraw plant material with 10 times of its weight of distilled water andkeeping it overnight. A viscous solution is obtained, which is passedthrough a muslin cloth. The gum or mucilage is precipitated by additionof 95% by weight of ethanol in a ratio of about 1:1 by continuousstirring. A coagulated mass is obtained, which is subsequently dried inan oven at 40 to 45° C., powdered by passing through a sieve and storedin an airtight container.

In the nutritional product of the invention, it is further preferredthat the above specified aqueous solution of a food grade biopolymerfurther comprises rigid particles. In the context of this disclosure,the term “rigid” means that the particles show no measurable deformationunder the forces encountered during swallowing. Such particles maypreferably be selected from sucrose crystals, cocoa particles,microcrystalline cellulose particles, starch and modified starchgranules, protein particles, and any combination thereof.

The thus defined rigid particles may have a size of between 1 and 100micrometers, more preferably between 1.5 and 80 micrometers, and mostpreferably between 2 and 50 micrometers.

In the present invention, the particle size is expressed in terms of theaverage equivalent particle diameter. In the context of this disclosure,the equivalent particle diameter refers to the diameter of a sphere ofequal volume as the particle volume, which may be determined by anysuitable method known in the art. Preferably, the equivalent particlediameter is determined by laser diffraction, e.g. using a Malvern®Mastersizer instrument. Further, in this context, the average equivalentparticle diameter is based on a number average, which is to beunderstood as the arithmetic mean of all particle diameters in a sample,usually reported as D[1,0].

Moreover, it is particularly preferred that the rigid particles have anelongated shape, which means that they have an aspect ratio of largerthan 1.0.

It is further preferred that the above rigid particles are comprised inthe aqueous solution of a food grade biopolymer in an amount of between5 and 80 vol.−%, more preferably between 10 and 70 vol.−%, and mostpreferably between 15 and 50 vol.−%. In the context of this disclosure,vol.−% signifies the percentage of the volume of all rigid particles inthe solution as a whole, per total volume of said solution.

The presence of such rigid particles in the nutritional product of theinvention was found to locally enhance extensional flow and to therebyincrease extensional stresses, leading to a higher apparent extensionalviscosity of said product.

The nutritional products of the invention may further comprise highmolecular weight proteins that may include, for example,collagen-derived proteins such as gelatin, plant proteins such aspotato, pea, lupin, etc., or other proteins of sufficiently highmolecular weight (MW=100 kDa and above).

In a preferred embodiment, the nutritional product of the invention maycomprise a source of dietary protein including, but not limited toanimal protein (such as meat protein or egg protein), dairy protein(such as casein, caseinates (e.g., all forms including sodium, calcium,potassium caseinates), casein hydrolysates, whey (e.g., all formsincluding concentrate, isolate, demineralized), whey hydrolysates, milkprotein concentrate, and milk protein isolate)), vegetable protein (suchas soy protein, wheat protein, rice protein, and pea protein), orcombinations thereof. In an embodiment, the protein source is selectedfrom the group consisting of whey, chicken, corn, caseinate, wheat,flax, soy, carob, pea, or combinations thereof.

In another embodiment, the nutritional products of the invention maycomprise a source of carbohydrates. Any suitable carbohydrate may beused in the present nutritional products including, but not limited to,sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrin,modified starch, amylose starch, tapioca starch, corn starch orcombinations thereof.

In another embodiment of the invention, the nutritional products includea source of fat. The source of fat may include any suitable fat or fatmixture. For example, the fat source may include, but is not limited to,vegetable fat (such as olive oil, corn oil, sunflower oil, rapeseed oil,hazelnut oil, soy oil, palm oil, coconut oil, canola oil, lecithins, andthe like), animal fats (such as milk fat) or combinations thereof.

In a preferred embodiment of the invention, the nutritional productsfurther include one or more prebiotics. Non-limiting examples ofprebiotics include acacia gum, alpha glucan, arabinogalactans, betaglucan, dextrans, fructooligosaccharides, fucosyllactose,galactooligosaccharides, galactomannans, gentiooligosaccharides,glucooligosaccharides, guar gum, inulin, isomaltooligosaccharides,lactoneotetraose, lactosucrose, lactulose, levan, maltodextrins, milkoligosaccharides, partially hydrolyzed guar gum, pecticoligosaccharides,resistant starches, retrograded starch, sialooligosaccharides,sialyllactose, soyoligosaccharides, sugar alcohols,xylooligosaccharides, their hydrolysates, or combinations thereof.

In another preferred embodiment of the invention, the nutritionalproducts further include one or more probiotics. Non-limiting examplesof probiotics include Aerococcus, Aspergillus, Bacteroides,Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus,Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus,Micrococcus, Mucor, Oenococcus, Pediococcus, Penicillium,Peptostrepococcus, Pichia, Propionibacterium, Pseudocatenulatum,Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis,Weissella, or combinations thereof.

Moreover, preferably, one or more amino acids may also be present in theinventive nutritional products. Non-limiting examples of amino acidsinclude alanine, arginine, asparagine, aspartate, citrulline, cysteine,glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyserine,hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine,phenylalanine, proline, serine, taurine, threonine, tryptophan,tyrosine, valine, or combinations thereof.

In further embodiments, the nutritional products further include one ormore synbiotics, sources of 03-3 fatty acids, and/or phytonutrients. Asused herein, a synbiotic is a supplement that contains both a prebioticand a probiotic that work together to improve the microflora of theintestine. Non-limiting examples of sources of ω-3 fatty acids suchα-linolenic acid (“ALA”), docosahexaenoic acid (“DHA”) andeicosapentaenoic acid (“EPA”) include fish oil, krill, poultry, eggs, orother plant or nut sources such as flax seed, walnuts, almonds, algae,modified plants, etc. Non-limiting examples of phytonutrients includequercetin, curcumin and limonin and combinations thereof.

According to the invention, one or more antioxidants may also be presentin the nutritional products. Non-limiting examples of antioxidantsinclude carotenoids, coenzyme Q10 (“CoQ10”), flavonoids, glutathioneGoji (wolfberry), hesperidin, lactowolfberry, lignan, lutein, lycopene,polyphenols, selenium, vitamin A, vitamin B₁, vitamin B₆, vitamin B₁₂,vitamin C, vitamin D, vitamin E, zeaxanthin, or combinations thereof.

The nutritional products may also include fiber or a blend of differenttypes of fiber. The fiber blend may contain a mixture of soluble andinsoluble fibers. Soluble fibers may include, for example,fructooligosaccharides, acacia gum, inulin, etc. Insoluble fibers mayinclude, for example, pea outer fiber.

The nutritional products of the invention may also include otherfunctional ingredients including chitosans and protein aggregates.Chitosans are linear polysaccharides composed of randomly distributedβ-(1-4)-linked D-glucosamine (deacetylated unit) andN-acetyl-D-glucosame (acetylated unit). Among other potential benefits,chitosans have natural antibacterial properties, aid in drug delivery,and are known to rapidly clot blood. Protein aggregates are coalescencesof miss-folded proteins driven by interactions between solvent-exposedhydrophobic surfaces that are normally buried within a protein'sinterior.

Another aspect of the invention relates to methods for making the abovenutritional product. The methods include providing a solution of a foodgrade biopolymer capable of providing to the nutritional product a shearviscosity of less than about 100 mPas, preferably of less than about 50mPas, when measured at a shear rate of 50 s⁻¹, and a relaxation time,determined by a Capillary Breakup Extensional Rheometry (CaBER)experiment, of more than 10 ms (milliseconds) at a temperature of 20° C.In an embodiment, shear viscosity is at least about 1 mPas, preferablyfrom at least about 1 mPas to less than about 50 mPas, more preferablyfrom at least 5 mPas to less than 20 mPas, when measured at a shear rateof 50 s⁻¹. In a preferred embodiment of the inventive method, relaxationtime is less than about 2000 ms, preferably from about 20 ms to about1000 ms, more preferably from about 50 ms to about 500 ms, and mostpreferably from about 100 ms to about 200 ms. In another preferredembodiment, the filament diameter of the nutritional product decreasesless than linearly, and preferably exponentially in time during a CaBERexperiment. In yet another preferred embodiment, the aqueous solutioncomprises a food grade biopolymer in a concentration of from at least0.01 wt % to 25 wt %, preferably from at least 0.1 wt % to 15 wt %, andmost preferably from at least 1 wt % to 10 wt %. In a furtherembodiment, the method includes further diluting the nutritionalproduct, preferably in an aqueous dilution ranging from 2:1 to 50:1,more preferably from 3:1 to 20:1 and most preferably from 5:1 to 10:1.

In yet another aspect of the invention, a method for improving thecohesiveness of a nutritional product is provided. This method includesadding to a nutritional product a solution of a food grade biopolymercapable of providing to the nutritional product a shear viscosity ofless than about 100 mPas, preferably of less than about 50 mPas, whenmeasured at a shear rate of 50 s⁻¹, and a relaxation time, determined bya Capillary Breakup Extensional Rheometry (CaBER) experiment, of morethan 10 ms (milliseconds) at a temperature of 20° C., such that thenutritional product does not break-up during consumption of thenutritional product. Preferably, shear viscosity is at least about 1mPas, more preferably from at least about 1 mPas to less than about 50mPas, and most preferably from at least 5 mPas to less than 20 mPas,when measured at a shear rate of 50 s⁻¹. It is also preferred thatrelaxation time is less than about 2000 ms, more preferably from about20 ms to about 1000 ms, even more preferably from about 50 ms to about500 ms, and most preferably from about 100 ms to about 200 ms. Inanother preferred embodiment of this aspect of the invention, thefilament diameter of the nutritional product decreases less thanlinearly, and preferably exponentially in time during a CaBERexperiment. In yet another preferred embodiment, the aqueous solutioncomprises a food grade biopolymer in a concentration of from at least0.01 wt % to 25 wt %, preferably from at least 0.1 wt % to 15 wt %, andmost preferably from at least 1 wt % to 10 wt %. In a further preferredembodiment, the nutritional product is further diluted, preferably in anaqueous dilution ranging from 2:1 to 50:1, more preferably from 3:1 to20:1 and most preferably from 5:1 to 10:1.

The present invention further provides methods for promoting safeswallowing of food boluses. These methods include adding to anutritional product a solution of a food grade biopolymer capable ofproviding to the nutritional product a shear viscosity of less thanabout 100 mPas, preferably of less than about 50 mPas, when measured ata shear rate of 50 s⁻¹, and a relaxation time, determined by a CapillaryBreakup Extensional Rheometry (CaBER) experiment, of more than 10 ms(milliseconds) at a temperature of 20° C., such that the nutritionalproduct does not break-up during consumption of the nutritional product.Preferably, shear viscosity is at least about 1 mPas, more preferablyfrom at least about 1 mPas to less than about 50 mPas, and mostpreferably from at least 5 mPas to less than 20 mPas, when measured at ashear rate of 50 s⁻¹. It is also preferred that relaxation time is lessthan about 2000 ms, more preferably from about 20 ms to about 1000 ms,even more preferably from about 50 ms to about 500 ms, and mostpreferably from about 100 ms to about 200 ms. In another preferredembodiment of this aspect of the invention, the filament diameter of thenutritional product decreases less than linearly, and preferablyexponentially in time during a CaBER experiment. In yet anotherpreferred embodiment, the aqueous solution comprises a food gradebiopolymer in a concentration of from at least 0.01 wt % to 25 wt %,preferably from at least 0.1 wt % to 15 wt %, and most preferably fromat least 1 wt % to 10 wt %. In a further preferred embodiment, thenutritional product is further diluted, preferably in an aqueousdilution ranging from 2:1 to 50:1, more preferably from 3:1 to 20:1 andmost preferably from 5:1 to 10:1.

In yet another aspect of the invention, methods for treating a patienthaving a swallowing disorder are provided. These methods includeadministering to a patient in need of same a nutritional productcomprising an aqueous solution of a food grade biopolymer capable ofproviding to the nutritional product a shear viscosity of less thanabout 100 mPas, preferably of less than about 50 mPas, when measured ata shear rate of 50 s⁻¹, and a relaxation time, determined by a CapillaryBreakup Extensional Rheometry (CaBER) experiment, of more than 10 ms(milliseconds) at a temperature of 20° C., such that the nutritionalproduct does not break-up during consumption of the nutritional product.Preferably, shear viscosity is at least about 1 mPas, more preferablyfrom at least about 1 mPas to less than about 50 mPas, and mostpreferably from at least 5 mPas to less than 20 mPas, when measured at ashear rate of 50 s⁻¹. It is also preferred that relaxation time is lessthan about 2000 ms, more preferably from about 20 ms to about 1000 ms,even more preferably from about 50 ms to about 500 ms, and mostpreferably from about 100 ms to about 200 ms. In another preferredembodiment of this aspect of the invention, the filament diameter of thenutritional product decreases less than linearly, and preferablyexponentially in time during a CaBER experiment. In yet anotherpreferred embodiment, the aqueous solution comprises a food gradebiopolymer in a concentration of from at least 0.01 wt % to 25 wt %,preferably from at least 0.1 wt % to 15 wt %, and most preferably fromat least 1 wt % to 10 wt %. In a further preferred embodiment, thenutritional product is further diluted, preferably in an aqueousdilution ranging from 2:1 to 50:1, more preferably from 3:1 to 20:1 andmost preferably from 5:1 to 10:1.

It is particularly preferred in any one of the above methods that thefood grade biopolymer is selected from the group consisting of botanicalhydrocolloids, microbial hydrocolloids, animal hydrocolloids, algaehydrocolloids and any combination thereof.

It is further preferred that the algae hydrocolloids are selected fromthe group consisting of agar, carrageenan, alginate, or any combinationsthereof. Moreover, the microbial hydrocolloids are preferably selectedfrom the group consisting of xanthan gum, gellan gum, curdlan gum, orany combinations thereof. Furthermore, the botanical hydrocolloids arepreferably selected from the group consisting of plant-extracted gums,plant-derived mucilages and combinations thereof.

In any one of the above methods of the invention, the plant-extractedgums may preferably be selected from the group consisting of okra gum,konjac mannan, tara gum, locust bean gum, guar gum, fenugreek gum,tamarind gum, cassia gum, acacia gum, gum ghatti, pectins, cellulosics,tragacanth gum, karaya gum, or any combinations thereof. In preferredembodiments, the plant-extracted gum is okra gum. Further, theplant-derived mucilages may preferably be selected from the groupconsisting of kiwi fruit mucilage, cactus mucilage (Ficus indica), chiaseed mucilage (Salvia hispanica), psyllium mucilage (Plantago ovata),mallow mucilage (Malva sylvestris), flax seed mucilage (Linumusitatissimum), marshmallow mucilage (Althaea officinalis), ribwortmucilage (Plantago lanceolata), mullein mucilage (Verbascum), cetrariamucilage (Lichen islandicus), or any combinations thereof. It is mostlypreferred that the plant-derived mucilage is kiwi fruit mucilage, whichis most preferably derived from the stem pith of kiwi fruit.

In preferred embodiments of the above referenced methods, the food gradebiopolymer is selected from okra gum and/or kiwi fruit mucilage, or acombination thereof.

In any one of the above methods of the invention, it is particularlypreferred that the aqueous solution of a food grade biopolymer furthercomprises rigid particles. Such particles may preferably be selectedfrom sucrose crystals, cocoa particles, microcrystalline celluloseparticles, starch and modified starch granules, protein particles, andany combination thereof.

Moreover, these rigid particles may have a size of between 1 and 100micrometers, more preferably between 2.5 and 80 micrometers, and mostpreferably between 5 and 50 micrometers. It is particularly preferredthat the rigid particles are elongated, which means that they have anaspect ratio of larger than 1.0.

It is further preferred that the thus defined rigid particles are addedto the aqueous solution of a food grade biopolymer according to theinvention in an amount of between 5 and 80 vol.−%, more preferablybetween 10 and 70 vol.−%, and most preferably between 15 and 50 vol.−%.In the context of this disclosure, vol.−% signifies the percentage ofthe volume of all rigid particles in the solution as a whole, per totalvolume of said solution.

In the above methods of the invention it is further preferred that thenutritional product comprises a source of dietary protein including, butnot limited to animal protein (such as meat protein or egg protein),dairy protein (such as casein, caseinates (e.g., all forms includingsodium, calcium, potassium caseinates), casein hydrolysates, whey (e.g.,all forms including concentrate, isolate, demineralized), wheyhydrolysates, milk protein concentrate, and milk protein isolate)),vegetable protein (such as soy protein, wheat protein, rice protein, andpea protein), or combinations thereof. In an embodiment, the proteinsource is selected from the group consisting of whey, chicken, corn,caseinate, wheat, flax, soy, carob, pea, or combinations thereof.

In the above methods of the invention it is also preferred that thenutritional product comprises a source of carbohydrates. Any suitablecarbohydrate may be used in the present nutritional products including,but not limited to, sucrose, lactose, glucose, fructose, corn syrupsolids, maltodextrin, modified starch, amylose starch, tapioca starch,corn starch or combinations thereof.

The nutritional products may further include a source of fat. The sourceof fat may include any suitable fat or fat mixture. For example, the fatsource may include, but is not limited to, vegetable fat (such as oliveoil, corn oil, sunflower oil, rapeseed oil, hazelnut oil, soy oil, palmoil, coconut oil, canola oil, lecithins, and the like), animal fats(such as milk fat) or combinations thereof.

In preferred embodiments of the above methods according to theinvention, the nutritional products further include one or moreprebiotics. Non-limiting examples of prebiotics include acacia gum,alpha glucan, arabinogalactans, beta glucan, dextrans,fructooligosaccharides, fucosyllactose, galactooligosaccharides,galactomannans, gentiooligosaccharides, glucooligosaccharides, guar gum,inulin, isomaltooligosaccharides, lactoneotetraose, lactosucrose,lactulose, levan, maltodextrins, milk oligosaccharides, partiallyhydrolyzed guar gum, pecticoligosaccharides, resistant starches,retrograded starch, sialooligosaccharides, sialyllactose,soyoligosaccharides, sugar alcohols, xylooligosaccharides, theirhydrolysates, or combinations thereof.

In further preferred embodiments of the above methods according to theinvention, the nutritional products further include one or moreprobiotics. Non-limiting examples of probiotics include Aerococcus,Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium,Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus,Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus,Penicillium, Peptostrepococcus, Pichia, Propionibacterium,Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus,Streptococcus, Torulopsis, Weissella, or combinations thereof.

Moreover, preferably, one or more amino acids may also be present in theinventive nutritional products. Non-limiting examples of amino acidsinclude alanine, arginine, asparagine, aspartate, citrulline, cysteine,glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyserine,hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine,phenylalanine, proline, serine, taurine, threonine, tryptophan,tyrosine, valine, or combinations thereof.

In further embodiments of the inventive methods, the nutritionalproducts further include one or more synbiotics, sources of ω-3 fattyacids, and/or phytonutrients. As used herein, a synbiotic is asupplement that contains both a prebiotic and a probiotic that worktogether to improve the microflora of the intestine. Non-limitingexamples of sources of ω-3 fatty acids such α-linolenic acid (“ALA”),docosahexaenoic acid (“DHA”) and eicosapentaenoic acid (“EPA”) includefish oil, krill, poultry, eggs, or other plant or nut sources such asflax seed, walnuts, almonds, algae, modified plants, etc. Non-limitingexamples of phytonutrients include quercetin, curcumin and limonin andcombinations thereof.

In further preferred embodiments of the above methods according to theinvention, one or more antioxidants may also be present in thenutritional products. Non-limiting examples of antioxidants includecarotenoids, coenzyme Q10 (“Co Q10”), flavonoids, glutathione Goji(wolfberry), hesperidin, lactowolfberry, lignan, lutein, lycopene,polyphenols, selenium, vitamin A, vitamin B₁, vitamin B₆, vitamin B₁₂,vitamin C, vitamin D, vitamin E, zeaxanthin, or combinations thereof.

In these methods, the nutritional products may also include fiber or ablend of different types of fiber. The fiber blend may contain a mixtureof soluble and insoluble fibers. Soluble fibers may include, forexample, fructooligosaccharides, acacia gum, inulin, etc. Insolublefibers may include, for example, pea outer fiber.

In other embodiments of the above methods, the nutritional products ofthe invention may also include other functional ingredients includingchitosans and protein aggregates.

By using the improved nutritional products and methods of making andadministering same, the nutritional intake of dysphagic patients may beimproved by enabling them to swallow a wider variety of food andbeverage products safely and comfortably. Such advantages may beachieved by improving the cohesiveness of a food bolus, which lends tothe confidence of the patient in being able to consume a variety ofproducts without the food bolus breaking up and possibly being aspiratedby the patient. Such nutritional improvements may lead to an overallhealthier condition of the patient and prevent further health-relateddecline.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

1. A nutritional product comprising an aqueous solution of a food gradebiopolymer capable of providing to the nutritional product: a shearviscosity of less than about 100 mPas when measured at a shear rate of50 s⁻¹; and a relaxation time, determined by a Capillary BreakupExtensional Rheometry (CaBER) experiment, of more than 10 ms(milliseconds) at a temperature of 20° C.
 2. The nutritional productaccording to claim 1, wherein shear viscosity is at least about 1 mPaswhen measured at a shear rate of 50 s⁻¹.
 3. The nutritional productaccording to claim 1, wherein the relaxation time is less than about2000 ms at a temperature of 20° C.
 4. The nutritional product accordingto claim 1, wherein the filament diameter of the nutritional productdecreases less than linearly during a CaBER experiment.
 5. Thenutritional product according to claim 1, wherein the aqueous solutioncomprises a food grade biopolymer at a concentration of from at least0.01 wt % to 25 wt %.
 6. The nutritional product according to claim 1 indiluted form.
 7. The nutritional product according to claim 1, whereinthe food grade biopolymer is selected from the group consisting ofbotanical hydrocolloids, microbial hydrocolloids, animal hydrocolloids,algae hydrocolloids and combinations thereof.
 8. The nutritional productaccording to claim 7, wherein the algae hydrocolloids are selected fromthe group consisting of agar, carrageenan, alginate, and combinationsthereof.
 9. The nutritional product according to claim 7, wherein themicrobial hydrocolloids are selected from the group consisting ofxanthan gum, gellan gum, curdlan gum, and combinations thereof.
 10. Thenutritional product according to claim 7, wherein the botanicalhydrocolloids are selected from the group consisting of plant-extractedgums, plant-derived mucilages, and combinations thereof.
 11. Thenutritional product according to claim 10, wherein the plant-extractedgums are selected from the group consisting of okra gum, konjac mannan,tara gum, locust bean gum, guar gum, fenugreek gum, tamarind gum, cassiagum, acacia gum, gum ghatti, pectins, cellulosics, tragacanth gum,karaya gum, and combinations thereof.
 12. The nutritional productaccording to claim 10, wherein the plant-derived mucilages are selectedfrom the group consisting of kiwi fruit mucilage, cactus mucilage, chiaseed mucilage, psyllium mucilage, mallow mucilage, flax seed mucilage,marshmallow mucilage, ribwort mucilage, mullein mucilage, cetrariamucilage, and combinations thereof.
 13. The nutritional productaccording to claim 1, wherein the food grade biopolymer is selected fromthe group consisting of okra gum, kiwi fruit mucilage, and combinationsthereof.
 14. The nutritional product according to claim 12, wherein thekiwi fruit mucilage is derived from the stem pith of kiwi fruit.
 15. Thenutritional product according to claim 1, wherein the aqueous solutioncomprises rigid particles.
 16. The nutritional product according toclaim 1 comprising a prebiotic selected from the group consisting ofacacia gum, alpha glucan, arabinogalactans, beta glucan, dextrans,fructooligosaccharides, fucosyllactose, galactooligosaccharides,galactomannans, gentiooligosaccharides, gluco-oligosaccharides, guargum, inulin, isomaltooligosaccharides, lactoneotetraose, lactosucrose,lactulose, levan, maltodextrins, milk oligosaccharides, partiallyhydrolyzed guar gum, pecticoligosaccharides, resistant starches,retrograded starch, sialooligosaccharides, sialyllactose,soyoligosaccharides, sugar alcohols, xylooligosaccharides, theirhydrolysates, and combinations thereof.
 17. The nutritional productaccording to claim 1 comprising a probiotic selected from the groupconsisting of Aerococcus, Aspergillus, Bacteroides, Bifidobacterium,Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium,Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Micrococcus,Mucor, Oenococcus, Pediococcus, Penicillium, Peptostrepococcus, Pichia,Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces,Staphylococcus, Streptococcus, Torulopsis, Weissella, and combinationsthereof.
 18. The nutritional product according to claim 1 comprising anamino acid selected from the group consisting of alanine, arginine,asparagine, aspartate, citrulline, cysteine, glutamate, glutamine,glycine, histidine, hydroxyproline, hydroxyserine, hydroxytyrosine,hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine,proline, serine, taurine, threonine, tryptophan, tyrosine, valine, andcombinations thereof.
 19. The nutritional product according to claim 1comprising a fatty acid selected from the group consisting ofdocosahexaenoic acid, eicosapentaenoic acid, and combinations thereof.20. The nutritional product according to claim 19, wherein the fattyacid is derived from a source selected from the group consisting of fishoil, krill, plant sources containing ω-3 fatty acids, flaxseed, walnut,algae, and combinations thereof.
 21. The nutritional product accordingto claim 1 comprising a phytonutrient selected from the group consistingof flavanoids, allied phenolic compounds, polyphenolic compounds,terpenoids, alkaloids, sulphur-containing compounds, and combinationsthereof.
 22. The nutritional product according to claim 21, wherein thephytonutrient is selected from the group consisting of carotenoids,plant sterols, quercetin, curcumin, limonin, and combinations thereof.23. The nutritional product according to claim 1 comprising anantioxidant selected from the group consisting of astaxanthin,carotenoids, coenzyme Q10 (“CoQ10”), flavonoids, glutathione Goji(wolfberry), hesperidin, lactowolfberry, lignan, lutein, lycopene,polyphenols, selenium, vitamin A, vitamin C, vitamin E, zeaxanthin, andcombinations thereof.
 24. The nutritional product according to claim 1,wherein the nutritional product is in an administrable form selectedfrom the group consisting of pharmaceutical formulations, nutritionalformulations, dietary supplements, functional food and beverageproducts, and combinations thereof.
 25. A method for treating aswallowing disorder comprising the step of administering a nutritionalproduct comprising an aqueous solution of a food grade biopolymercapable of providing to the nutritional product: a shear viscosity ofless than about 100 mPas when measured at a shear rate of 50 s⁻¹; and arelaxation time, determined by a Capillary Breakup Extensional Rheometry(CaBER) experiment, of more than 10 ms (milliseconds) at a temperatureof 20° C. to an individual in need of same.
 26. A method for promotingsafe swallowing of nutritional products in a patient in need of samecomprising the step of administering a nutritional product comprising anaqueous solution of a food grade biopolymer capable of providing to thenutritional product: a shear viscosity of less than about 100 mPas whenmeasured at a shear rate of 50 s⁻¹; and a relaxation time, determined bya Capillary Breakup Extensional Rheometry (CaBER) experiment, of morethan 10 ms (milliseconds) at a temperature of 20° C. to an individual inneed of same.
 27. A method for mitigating the risks of aspiration duringswallowing of nutritional products in a patient in need of samecomprising the step of administering a nutritional product comprising anaqueous solution of a food grade biopolymer capable of providing to thenutritional product: a shear viscosity of less than about 100 mPas whenmeasured at a shear rate of 50 s⁻¹; and a relaxation time, determined bya Capillary Breakup Extensional Rheometry (CaBER) experiment, of morethan 10 ms (milliseconds) at a temperature of 20° C. to an individual inneed of same.
 28. A method for making a nutritional product, the methodcomprising providing an aqueous solution of a food grade biopolymer thatprovides to the nutritional product: a shear viscosity of less thanabout 100 mPas, when measured at a shear rate of 50 s⁻¹, and arelaxation time, determined by a Capillary Breakup Extensional Rheometry(CaBER) experiment, of more than 10 ms (milliseconds) at a temperatureof 20° C.
 29. The method according to claim 28, wherein shear viscosityis at least about 1 mPas when measured at a shear rate of 50 s⁻¹. 30.The method according to claim 28, wherein relaxation time is less thanabout 2000 ms.
 31. The method according to claim 28, wherein thefilament diameter of the nutritional product decreases less thanlinearly.
 32. The method according to claim 28, wherein the aqueoussolution comprises a food grade biopolymer in a concentration of from atleast 0.01 wt % to 25 wt %.
 33. The method according to claim 28,comprising the step of diluting the nutritional product.
 34. The methodaccording to claim 28, wherein the food grade biopolymer is selectedfrom the group consisting of botanical hydrocolloids, microbialhydrocolloids, animal hydrocolloids, algae hydrocolloids andcombinations thereof.
 35. The method according to claim 34, wherein thealgae hydrocolloids are selected from the group consisting of agar,carrageenan, alginate, and combinations thereof.
 36. The methodaccording to claim 34, wherein the microbial hydrocolloids are selectedfrom the group consisting of xanthan gum, gellan gum, curdlan gum, andcombinations thereof.
 37. The method according to claim 34, wherein thebotanical hydrocolloids are selected from the group consisting ofplant-extracted gums, plant-derived mucilages, and combinations thereof.38. The method according to claim 37, wherein the plant-extracted gumsare selected from the group consisting of okra gum, konjac mannan, taragum, locust bean gum, guar gum, fenugreek gum, tamarind gum, cassia gum,acacia gum, gum ghatti, pectins, cellulosics, tragacanth gum, karayagum, and combinations thereof.
 39. The method according to claim 37,wherein the plant-derived mucilages are selected from the groupconsisting of kiwi fruit mucilage, cactus mucilage, chia seed mucilage,psyllium mucilage, mallow mucilage, flax seed mucilage, marshmallowmucilage, ribwort mucilage, mullein mucilage, cetraria mucilage, andcombinations thereof.
 40. The method according to claim 28, wherein thefood grade biopolymer is selected from the group consisting of okra gum,kiwi fruit mucilage and combinations thereof.
 41. The method accordingto claim 39, wherein the kiwi fruit mucilage is derived from the stempith of kiwi fruit.
 42. The method according to claim 28, wherein theaqueous solution comprises rigid particles.
 43. The method according toclaim 28, comprising adding to the nutritional product a prebioticselected from the group consisting of acacia gum, alpha glucan,arabinogalactans, beta glucan, dextrans, fructooligosaccharides,fucosyllactose, galactooligosaccharides, galactomannans,gentiooligosaccharides, glucooligosaccharides, guar gum, inulin,isomaltooligosaccharides, lactoneotetraose, lactosucrose, lactulose,levan, maltodextrins, milk oligosaccharides, partially hydrolyzed guargum, pecticoligosaccharides, resistant starches, retrograded starch,sialooligosaccharides, sialyllactose, soyoligosaccharides, sugaralcohols, xylooligosaccharides, their hydrolysates, and combinationsthereof.
 44. The method according to claim 28, comprising adding to thenutritional product a probiotic selected from the group consisting ofAerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida,Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus,Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus,Pediococcus, Penicillium, Peptostrepococcus, Pichia, Propionibacterium,Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus,Streptococcus, Torulopsis, Weissella, and combinations thereof.
 45. Themethod according to claim 28, comprising adding to the nutritionalproduct an amino acid selected from the group consisting of alanine,arginine, asparagine, aspartate, citrulline, cysteine, glutamate,glutamine, glycine, histidine, hydroxyproline, hydroxyserine,hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine,phenylalanine, proline, serine, taurine, threonine, tryptophan,tyrosine, valine, and combinations thereof.
 46. The method according toclaim 28, comprising adding to the nutritional product a fatty acidselected from the group consisting of docosahexaenoic acid,eicosapentaenoic acid, and combinations thereof.
 47. The methodaccording to claim 46, wherein the fatty acid is derived from a sourceselected from the group consisting of fish oil, hill, plant sourcescontaining ω-3 fatty acids, flaxseed, walnut, algae, and combinationsthereof.
 48. The method according to claim 28, comprising adding to thenutritional product a phytonutrient selected from the group consistingof flavanoids, allied phenolic compounds, polyphenolic compounds,terpenoids, alkaloids, sulphur-containing compounds, and combinationsthereof, and preferably selected from the group consisting ofcarotenoids, plant sterols, quercetin, curcumin, limonin, andcombinations thereof.
 49. The method according to claim 28, comprisingadding to the nutritional product an antioxidant selected from the groupconsisting of astaxanthin, carotenoids, coenzyme Q10 (“CoQ10”),flavonoids, glutathione Goji (wolfberry), hesperidin, lactowolfberry,lignan, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin C,vitamin E, zeaxanthin, and combinations thereof.
 50. The methodaccording to claim 28, comprising the step of formulating thenutritional product to be in an administrable form selected from thegroup consisting of pharmaceutical formulations, nutritionalformulations, dietary supplements, functional food and beverageproducts, and combinations thereof.